Inducing activation of ovarian follicles in order to achieve maturation is highly desirably from a research perspective but also within numerous fields of application. Primordial follicles could potentially serve as a source of oocytes for in vitro fertilization, but the ability to utilize activated and matured ovarian follicles for other applications, for instance post-chemotherapy or radiation treatment of cancer, is also of great importance. However, there is currently no means for primordial follicle activation, implying that a potentially vital source of oocyte material remains unexploited. In the light of the debate regarding in vitro fertilization, such considerations are increasingly important.
In clinics, if a woman's primordial follicles can not start to grow, i.e. to be activated from the dormant state, her follicles will not respond to hormones, such as follicle stimulating hormone (FSH). Therefore, the woman is infertile, and she can not use her own oocytes for in vitro fertilization. Currently, as abovementioned, there is no technique to use primordial follicles as sources of oocytes for in vitro fertilization. Thus, there is a need in the art to develop methods for inducing either in vivo and/or in vitro activation and maturation of ovarian follicles for various applications.
Prior art describes the lipid kinases phosphatidylinositol 3-kinases (PI3Ks), which phosphorylate the 3′-OH group on the inositol ring of inositol phospholipids. PTEN (phosphatase and tensin homolog deleted on chromosome ten), a lipid phosphatase, reverses this process and thus functions as a major negative regulator of PI3K action (Cantley, Science 2002, 296: 1655-1657.).